Search Results (2)

This study tested the hypothesis that the increases in salivary and plasma [NO₂⁻] after dietary NO₃⁻ supplementation would be greater when oral temperature and pH were independently elevated, and increased further when oral temperature and pH were elevated concurrently. Seven healthy males (mean ± SD, age 23 ± 4 years) ingested 70 mL of beetroot juice concentrate (BR, which provided ~6.2 mmol NO₃⁻) during six separate laboratory visits. In a randomised crossover experimental design, salivary and plasma [NO₃⁻] and [NO₂⁻] were assessed at a neutral oral pH with a low (T_Lo-pH_Norm), intermediate (T_Mid-pH_Norm), and high (T_Hi-pH_Norm) oral temperature, and when the oral pH was increased at a low (T_Lo-pH_Hi), intermediate (T_Mid-pH_Hi), and high (T_Hi-pH_Hi) oral temperature. Compared with the T_Mid-pH_Norm condition (976 ± 388 µM), the mean salivary [NO₂⁻] 1–3 h post BR ingestion was higher in the T_Mid-pH_Hi (1855 ± 423 µM), T_Hi-pH_Norm (1371 ± 653 µM), T_Hi-pH_Hi (1792 ± 741 µM), T_Lo-pH_Norm (1495 ± 502 µM), and T_Lo-pH_Hi (2013 ± 662 µM) conditions, with salivary [NO₂⁻] also higher at a given oral temperature when the oral pH was increased (p < 0.05). Plasma [NO₂⁻] was higher 3 h post BR ingestion in the T_Mid-pH_Hi, T_Hi-pH_Hi, and T_Lo-pH_Hi conditions, but not the T_Lo-pH_Norm and T_Hi-pH_Norm conditions, compared with T_Mid-pH_Norm (p < 0.05). Therefore, despite ingesting the same NO₃⁻ dose, the increases in salivary [NO₂⁻] varied depending on the temperature and pH of the oral cavity, while the plasma [NO₂⁻] increased independently of oral temperature, but to a greater extent at a higher oral pH. Full article

This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for C_max (6.5 ± 2.0) and AUC_0–24 (4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t_1/2 plasma = 10.0 ± 2.8 h, t_1/2 saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient’s compliance to the treatment regimen in upcoming clinical trials of ATB. Full article